1. Field of the Invention
The present invention relates to a CD4T cell vaccine which can induce an antigen-specific cytotoxic T lymphocyte (CTL) response, and a use thereof.
2. Discussion of Related Art
Studies on cancer immunotherapy have been focused on activation of both congenital immunity and adoptive immunity, particularly, on an anticancer T cell response of recognizing a target cell and, on some occasions, eliminating the target cell to prevent, regulate, and treat several kinds of infections and malignant diseases. A cytotoxic CD8T cell is a major immune system effector capable of recognizing and destroying a tumor cell through numerous cell killing mechanisms. Activation of the CD8 T cell requires involvement of a T cell receptor and an allogeneic peptide major histocompatibility complex (pMHC) class I and also a costimulatory signal. The tumor cell seems to express a MHC molecule and a costimulatory ligand at an insufficient level, and, thus, it is necessary to manipulate a cellular adjuvant such as a dendritic cell in order to induce or increase an appropriate tumor-reactive CD8T cell response.
The dendritic cell (DC) is a very effective and specialized antigen-presenting cell since it can express a MHC molecule and a costimulatory ligand at a high level. A dendritic cell loaded with a tumor-associated antigen for clinical application has already been studied; DC-based cell vaccines are the choice important in the current cancer immunotherapy strategies against various tumors. In spite of their high efficiency in causing an antigen-specific T cell response in vivo, the DC has a serious shortcoming as a cellular adjuvant since it is present in a human peripheral blood cell at a low ratio (0.1 to 0.5%) and it is necessarily difficult to obtain DC sufficient for clinical application. In order to identify a reliable source for an autologous APC (Antigen-Presenting Cell) as an alternative to the DC for immunotherapy, some researchers studied other autologous cells which can be obtained from a small amount of peripheral blood since it is possible to easily proliferate and obtain pure allogeneic groups. The other researchers and the inventors of the present invention exhibited that B cells activated in vitro by treatment with inflammatory cytokine, CD40L, and toll-like receptor ligands can induce effective T cell priming and therapeutic anti-tumor immunity in vivo. According to another report, an activated human γδ T cell exhibits an effective antigen-presenting activity similar to DC activity that promotes proliferation and differentiation of a naive T cell. A CD4 T cell also induced a functional memory CD8 T cell response. According to the prior report, direct cross-priming by peptide-loaded lymphocytes exhibited that a memory cytotoxic T cell response takes place in a mouse model. Another study demonstrated that a DC-stimulated CD4 T cell obtains pMHC-I and costimulatory CD80, CD40, OX40L and 4-1BBL from a bystander antigen-presenting DC, promotes a central memory CD8 T cell response and induces secretion of IL-2, and anti-tumor immunity mediated by CD40L and CD80 signal transduction. Further, a human CD4 T cell representing a viral epitope induces a functional virus-specific memory CD8 T cell response.
Nonetheless, a cell vaccine using a CD4 T cell which can directly stimulate a naive CD8 T cell similar to a natural APC in a tumor model has not been developed.